Embryonic Veins Research Articles

Venous Anomalies in Overgrowth Syndromes

Overgrowth syndromes, particularly within the PIK3CA-related overgrowth syndrome (PROS)spectrum, are commonly associated with venous anomalies. The anomalies include spongiform venous malformations and persistent embryonic veins, such as the lateral marginal vein (of Servelle). The anomalous veins pose a significant risk of thromboembolic disease and should be occluded, preferably earlier in life. A thorough understanding of the conditions, anatomy, and interdisciplinary treatment of these complex anomalies is essential for optimal management. This review explores the clinical and imaging diagnosis of overgrowth syndromes and techniques for assessing and treating associated venous anomalies, particularly the endovenous closure of anomalous veins

Effects of neratinib on angiogenesis and the early stage of the embryo using chicken embryo as a model.

Angiogenesis is the process of forming new blood capillaries from pre-existing vessels. Even though it is essential during normal development, it plays a major role in cancer progression. Neratinib is a pan-human epidermal growth factor receptor (HER) inhibitor that has recently been approved for the treatment of HER2-positive breast cancer. However, its effects on angiogenesis and embryogenesis remain unknown. This study examined the antiangiogenic effects of neratinib using the chorioallantoic membrane (CAM) of chicken embryos. We also evaluated neratinib's toxicity during the early stages of normal development using the chicken embryos, primary embryonic fibroblasts (EFBs), and human umbilical vein endothelial cells (HUVEC). Our findings revealed that neratinib significantly inhibited the CAM angiogenesis compared to controls by reducing vessel percentage area and the average vessel length. Furthermore, neratinib downregulated vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. At lower concentrations, neratinib was well-tolerated during early stages of normal development. Additionally, EFBs treated with neratinib showed no morphological or viability changes when compared to controls. However, at the highest concentration tested, neratinib treatment reduced HUVEC cell viability. This effect may be associated with the dysregulation of key apoptotic genes, including caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 (Bcl2) gene. Our findings indicate a novel potential application of neratinib as an antiangiogenic agent, exhibiting tolerable toxicity in the early stages of embryogenesis.

A Twisted Tale of Vein of Galen Aneurysmal Malformation

AbstractThis illustration presents a three-dimensional representation of the vascular structure of the vein of Galen aneurysmal malformation (VGAM), which is a rare congenital brain vascular abnormality characterized by the enlargement of the embryonic precursor of the vein of Galen—specifically, the median prosencephalic vein of Markowski. VGAM constitutes an arteriovenous fistula formed between the deep choroidal arteries and the embryonic median prosencephalic vein. Its development initiates early but is typically detectable via sonography only during the second- or third-trimester of gestation. The comprehensive assessment of the vascular anatomy of VGAM necessitates the examination of both the incoming (afferent) and outgoing (efferent) vessels.

Update on the Vein of Galen Aneurysmal Malformation : Disease Concept and Genetics.

Vein of Galen aneurysmal malformation is one of important pediatric arteriovenous shunt diseases, especially among neonates and infants. Here, early history of the disease identification, basic pathoanatomy with a focus on the embryonic median prosencephalic vein, classification and differential diagnoses, and recent genetic studies are reviewed.

The development of early human lymphatic vessels as characterized by lymphatic endothelial markers

Lymphatic vessel development studies in mice and zebrafish models have demonstrated that lymphatic endothelial cells (LECs) predominantly differentiate from venous endothelial cells via the expression of the transcription factor Prox1. However, LECs can also be generated from undifferentiated mesoderm, suggesting potential diversity in their precursor cell origins depending on the organ or anatomical location. Despite these advances, recapitulating human lymphatic malformations in animal models has been difficult, and considering lymphatic vasculature function varies widely between species, analysis of development directly in humans is needed. Here, we examined early lymphatic development in humans by analyzing the histology of 31 embryos and three 9-week-old fetuses. We found that human embryonic cardinal veins, which converged to form initial lymph sacs, produce Prox1-expressing LECs. Furthermore, we describe the lymphatic vessel development in various organs and observe organ-specific differences. These characterizations of the early development of human lymphatic vessels should help to better understand the evolution and phylogenetic relationships of lymphatic systems, and their roles in human disease.

Variants of the Inferior Vena Cava

Abstract Abnormalities of the inferior vena cava (IVC) and its tributaries are rare anomalies detected more frequently by computed tomography scans with intravenous contrast. Its importance lies in identifying them by the possible clinical and surgical implications. They originate from the persistence or regression of the three embryonic veins (posterior cardinal, subcardinal, and supracardinal) and their anastomosis. There are three cases, the first with double IVC type I, which has a prevalence of 0.2%–3%. The second case has a left vena cava, which has a 0.2%–0.5% prevalence. The third case is with retroaortic left renal vein, which has a prevalence of 3.4%.

Structured magnetic resonance imaging-based characterization of the marginal vein reveals limits of the Weber-classification.

Background: The marginal vein (MV) is a persisting embryonic vein located at the lateral aspect of the lower limb. The Weber-classification, which was developed on the basis of phlebography in the 1990s, is the only existing classification system for this rare disease. Aim of this study was the structured characterization of the lateral marginal vein (MV) using magnetic resonance imaging (MRI) and evaluation of the applicability of the Weber-classification. Patients and methods: Institutional Review Board approval was obtained for this retrospective, single-center study. All patients who underwent contrast-enhanced MRI (using a prospectively determined protocol) of the untreated MV were included. MV anatomy and associated findings were characterized in a structured way taking into account the criteria of the Weber-classification for MV: inflow, outflow and extension. If three criteria of the Weber-classification were fulfilled the MV was categorized as "classifiable according to Weber". The MV was categorized as "partially classifiable according to Weber", if two criteria were met and as "not classifiable according to Weber" if less than two criteria were applicable. Results: 56 imaging studies of 58 MV (7 thoracoabdominal, 51 lower extremities) were reviewed. 18/51 MV of the lower extremities were "classifiable" according to the Weber-classification. 33/51 lower extremity MV were not definitely categorized according to the Weber-classification: 19/51 MV were "partially classifiable" and 14/51 MV were "not classifiable". 30/51 MV presented with hypoplastic, 1/51 with aplastic deep venous system. 34/51 lower extremity and 6/7 thoracoabdominal MV were associated with an additional vascular malformation (VM). Conclusions: MRI is suitable for detailed anatomic characterization of the MV and reveals additional therapy relevant findings like associated VM. The Weber-classification was not applicable in most cases, reflecting its limits and the heterogeneity of this rare disease. Structured reports rather than an obsolete classification system should be preferred for MRI of the MV.

Galen's Ampulla Aneurysm: A Case Report

Introduction: Galen's vein aneurysm is a rare complex intracranial arteriovenous malformation, associating pseudo-aneurysmal dilation of Galen's ampulla with one or more arteriovenous fistulas. The prognosis is often poor, with high mortality and a risk of neurological sequelae. Objective: To support the role of imaging in the diagnosis, with illustration by two observations collected within our Radiopediatrics department of the CHU Mohammed VI of Marrakech, having benefited from a cerebral angio-scanner. Case Report: 1st case:is an 18-month-old infant with no particular history presenting macrocrania with generalized seizures.2nd case:is also a 2-year-old infant, with the appearance of a vein in the suborbital groove for 6 months, with no other associated signs.3rd patientis a 1-year-old infant with macrocrania with signs of HTIC. 4th case6-month-old boy, presents with HTIC syndrome. Objective cerebral CT in the first three patients: a rounded median mass, in the pineal region behind the 3rd ventricle, slightly hyperdense in spontaneous contrast; CT angiography proves the vascular nature of the lesion by showing intense and homogeneous enhancement after injection of PDC, associated with dilation of the venous sinuses, and moderate passive triventricular hydrocephalus by compression of the aqueduct of Sylvius. The fourth patient benefited from a transfontanellar ultrasound which objectified an anechoic interhemispheric fusiform structure presenting a vascular flow to the color Doppler. Conclusion: The aneurysmal malformation of the Vein of Galen (AVGM) is a rare vascular malformation, specific to children, discovered ante or post natally, in fact only corresponds to a venous dilation draining an arterio-venous malformation, whose system afferent arterial comes from the carotid system or the vertebro-basilar axis; it results from the absence of differentiation in the mature arterio-venous system, between 7 and 12 SA, of a primitive, median embryonic vein which ......

The so-called absorption process of the pulmonary vein into the left atrium of the heart: a histological study using human embryos and fetuses.

Embryonic pulmonary veins (PVs) are believed to be absorbed into the left atrium (LA) to provide an adult morphology in which "four" veins drain separately into the atrium. Serial histological sections were obtained from 27 human embryos and fetuses. Between 5 and 6weeks, the four PVs joined together to form a trunk-like structure (initial spatium pulmonalis) that was larger than the initial LA (two-ostia pattern). The cardiac nerves ran inferiorly along the posterior aspect of the four veins, as well as the spatium. At and until 7weeks, the cardiac nerves were concentrated to elongate the nerve fold, and the latter separated the left PV trunk from the expanding LA (left spatium). Similarly, the right PV opened to a thick and deep LA recess (right spatium). At 8-12weeks, depending on the growth of the LA, the opening of the left and right PVs became distant, and the spatium was elongated transversely. The left spatium was enlarged to open widely to the proper left atrium in contrast to the right spatium pushed anteriorly by the right atrium. The three-ostia pattern was transiently observed because of the lost delimitation between the left spatium and proper atrium. The myocardium was thin in the left spatium behind the left atrial nerve fold, whereas the right spatium was tube-like with a thick myocardium. The four-ostia pattern seemed to be established at birth due to a drastically increased venous return from the lung, resulting in a flat smooth left atrial posterior wall.

Association of bilateral inferior vena cava with azygos and hemiazygos continuation and aortic coarctation in a child

Introduction. Developmental variations of the inferior cava vein (IVC) rarely cause symptoms, and they were detected during routine examinations performed for other reasons. The prevalence in the general population is between 0.07% and 8.7%. Various anomalies of the IVC can be seen depending on abnormal regression or abnormal persistence of embryonic veins. They are usually associated with more complex intracardiac and atrioventricular septal defects, partial anomalous pulmonary venous connection, and pulmonary atresia. Case Outline. We presented the 18th-month-old patient with double IVC, IVC interruption, azygos, and hemiazygos continuation associated with aortic coarctation. The vein malformation was discovered during percutaneous balloon angioplasty of the aortic re-coarctation and confirmed by using cross-sectional imaging modalities. Our patient had no symptoms of IVC malformation. Conclusion. In clinical practice, double IVC should be suspected in patients with recurrent pulmonary emboli. Another important point in practice is the identification of those anomalies to avoid potential complications of retroperitoneal surgery and cannulation during cardiac surgery

β-CD/PEI/PVA composite hydrogels with superior self-healing ability and antibacterial activity for wound healing

Bacterial infections in wounds often delay the healing process which threaten human health and life. The development of biocompatible hydrogels with antibacterial activity and self-healing to achieve excellent wound closure effectiveness is highly desirable in clinical applications. Herein, a new class of highly stretchable, biocompatible, and antibacterial hydrogel dressings called BPP hydrogel is designed and prepared by chemically cross-linking β-CD with PEI and then physically cross-linking with PVA. The BPP hydrogel exhibits superior properties including excellent antibacterial properties against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, good biocompatibility for mouse fibroblasts, mouse embryonic fibroblasts and human umbilical vein endothelial cells, outstanding deformability and self-healing performance to protect the wound completely even in special scenes such as pulling and bending. Besides, after damage, the broken BPP hydrogel could heal together, and the healed BPP hydrogel could be stretched to 150% breaking deformation. Furthermore, in vivo experiments further verify that BPP hydrogel has excellent sterilization and healing effect on infectious wounds. This work proves that BPP hydrogel would be a promising material for wound healing and has good prospect for clinical translation.

Treatment of venous malformations with tumescent-assisted sclero-embolic and ablative lasers (SEALs): Safe and effective long-term outcomes.

Perivascular infiltration of tumescent anaesthesia (TA) is an essential element of endovenous thermal ablative procedures employed to treat superficial venous disease. In addition to anaesthesia, TA is administered to achieve vessel wall approximation and to protect surrounding structures from thermal damage. However, its role in the treatment of venous malformations (VMs) has not been established. To assess the safety and efficacy of tumescent-assisted thermal and chemical ablative methods in the treatment of VMs. Adult and paediatric patients presenting with VMs were treated using a combination of endovenous laser ablation, foam embolo-sclerotherapy and liquid embolisation using n-BCA. All procedures were ultrasound-guided. Treatment outcomes were assessed in early and late follow-ups. To assess the efficacy of TA in achieving vessel wall approximation, cross-sectional lesional diameters were measured by ultrasound, before and after the administration of TA during endovenous procedures. In a 12month period, 22 patients recruited in the study presented with 27 VMs which included 23 extra-truncular lesions (16 subcutaneous and seven intramuscular) and four truncular anomalies. On average the subcutaneous lesions measured 5.5mm (1.9-24.5mm) in diameter, intramuscular lesions measured 9.2mm (5.9-15.1mm) and truncular anomalies measured 4.9mm (1.2-12mm) in diameter. Perivascular infiltration of TA resulted in a significant reduction in vessel calibre (90% reduction on average). Intramuscular VMs were less compressible with TA (69.2% reduction) compared to subcutaneous lesions (98% reduction). Truncular anomalies such as the embryonic marginal vein achieved complete approximation (100% reduction). Procedures were safely tolerated with no major complications such as thromboembolism, stroke, nerve damage or tissue necrosis. Most patients had significant clinical as well as ultrasonographic improvement. Tumescent-assisted endovenous laser ablation and foam sclerotherapy provides safe and effective outcomes in patients with a variety of VMs.

Imaging of vein of Galen malformation in late trimester

Vein of Galen malformation is a rare congenital vascular malformation due to the maldevelopment of the embryonic precursor median vein of Markowski. It results in significant morbidity and mortality in a fetus and neonate. Fetal ultrasound plays an important role in prenatal screening of fetuses to rule out development anomalies. Fetal Magnetic Resonance Imaging (MRI) plays a dual role both in diagnosis and periodical follow-up with identification of prognostically important complications of vein of Galen malformation. The combination of fetal ultrasound and fetal MRI provides a definite diagnosis during pregnancy thereby providing an opportunity to plan the delivery of the fetus and subsequent postnatal treatment. We are presenting a case of a 34 y female presented at 35 w period of gestation to the ultrasound unit of our hospital.

Prenatal ultrasonographic findings in Klippel-Trenaunay syndrome: A case report

BACKGROUNDKlippel-Trenaunay syndrome (KTS) is a rare congenital disorder. A detailed prenatal ultrasound examination plays an important role in the diagnosis of KTS and the subsequent counseling and follow-up of the patient. CASE SUMMARYA 25-year-old woman attended our department for a regular examination. The whole of the right lower extremity and right buttock were observed to be markedly thicker compared to the left one at 18 wk of gestation. However, the lengths of the right femur, tibia and fibula were in the normal range. No marked edema and fluid/cystic spaces were detected in the lower limbs. There were no other organ abnormalities. The vasculature in the right limb was visibly dilated, with much higher intensive blood flow signals. No congenital embryonic veins were visible in both limbs. The right lower limb exhibited much more hypertrophy compared to the left limb two weeks later. Amniocentesis and genetic tests showed normal results with 46 XX. Despite the normal karyotype, the family opted to terminate the pregnancy. The post-mortem examination confirmed asymmetric hypertrophy of the right limb in the fetus and revealed a large area of marked dark-purple superficial capillary malformations occupying the skin of the right lower extremity. The enlargement of veins and soft tissue hypertrophy were also seen on postnatal X-ray and Magnetic Resonance Imaging. Autopsy revealed severe congestion in the right lower limb. A final diagnosis of KTS was made.CONCLUSIONKTS may be diagnosed prenatally based on the typical features observed during ultrasound examination.

Lymphatic endothelial cell fate specification in the mammalian embryo: An historical perspective

Development of the mammalian lymphatic vasculature is a stepwise process requiring the specification of lymphatic endothelial cell progenitors in the embryonic veins, and their subsequent budding to give rise to most of the mature lymphatic vasculature. In mice, formation of the lymphatic vascular network starts inside the cardinal vein at around E9.5 when a subpopulation of venous endothelial cells gets committed into the lymphatic lineage by their acquisition of Prox1 expression. Identification of critical genes regulating lymphatic development facilitated the detailed cellular and molecular characterization of some of the cellular and molecular mechanisms regulating the early steps leading to the formation of the mammalian lymphatic vasculature. A better understanding of basic aspects of early lymphatic development, and the availability of novel tools and animal models has been instrumental in the identification of important novel functional roles of this vasculature network.

VP26.08: Vein of Galen aneurysmal malformation

Vein of Galen aneurysmal malformation is a rare complex malformation of the cerebral vascular system, characterised by the dilation of an embryonic vein precursor of the Galenian vein causing an arteriovenous shunt. It is developed in the embryonic period, sporadic, more common for male fetus. This vascular malformation is detected only half of times before birth, it often increases in size with advancing age and is associated with hydrocephalus, seizures, intracranial hemorrhage, heart failure and even resultant death. So early diagnosis and treatment is important in order to avoid such consequences. We report the case of a 31-year-old pregnant woman of 26 weeks, primiparous, with no obstetric or personal family history of interest. We found, at the second trimester morphological ultrasound, a cerebral vascular dilatation using the colour and pulsed Doppler which was isolated with no other cerebral or other organ malformations. First trimester ultrasound and serum markers were normal. Subsequently, a magnetic resonance was performed confirming the diagnosis. the pregnancy was carried to term with delivery by Caesarean section. Physical examination of the baby was unremarkable. The baby was called for post-natal evaluation at the radiology department on the second day and was scheduled for radiological embolisation of the aneurysm, the newborn died after that intervention. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function.

The lymphatic vascular system acts as the major transportation highway of tissue fluids, and its activation or impairment is associated with a wide range of diseases. There has been increasing interest in understanding the mechanisms that control lymphatic vessel formation (lymphangiogenesis) and function in development and disease. Here, we discuss recent insights into new players whose identification has contributed to deciphering the lymphatic regulatory code. We reveal how lymphatic endothelial cells, the building blocks of lymphatic vessels, utilize their transcriptional, post-transcriptional, and epigenetic portfolio to commit to and maintain their vascular lineage identity and function, with a particular focus on development.

Blood and lymphatic systems are segregated by the FLCN tumor suppressor

Blood and lymphatic vessels structurally bear a strong resemblance but never share a lumen, thus maintaining their distinct functions. Although lymphatic vessels initially arise from embryonic veins, the molecular mechanism that maintains separation of these two systems has not been elucidated. Here, we show that genetic deficiency of Folliculin, a tumor suppressor, leads to misconnection of blood and lymphatic vessels in mice and humans. Absence of Folliculin results in the appearance of lymphatic-biased venous endothelial cells caused by ectopic expression of Prox1, a master transcription factor for lymphatic specification. Mechanistically, this phenotype is ascribed to nuclear translocation of the basic helix-loop-helix transcription factor Transcription Factor E3 (TFE3), binding to a regulatory element of Prox1, thereby enhancing its venous expression. Overall, these data demonstrate that Folliculin acts as a gatekeeper that maintains separation of blood and lymphatic vessels by limiting the plasticity of committed endothelial cells.

Mechanochemical Endovenous Ablation of Varicose Veins in Pediatric Patients with Klippel-Trénaunay Syndrome: Feasibility, Safety, and Initial Results

PurposeTo evaluate feasibility, safety, and results of endovenous mechanochemical ablation (MOCA) for treatment of persistent embryonic and dysplastic veins in pediatric patients with Klippel-Trénaunay syndrome (KTS). Materials and MethodsThirteen MOCA procedures were performed in 11 patients (age range, 4–16 years) with KTS and symptomatic persistent embryonic or dysplastic veins during a 24-month period. All patients were evaluated with color Doppler (CD) ultrasound (US), contrast-enhanced MR imaging, and venography to assess the anatomy of the target vessels and patency of the deep venous system. All procedures were performed under general anesthesia with a ClariVein catheter and liquid sodium tetradecyl sulfate as the sclerosing agent. US and fluoroscopic guidance were used in all cases. Technical success rate, primary occlusion rate, adverse effects, and recanalization rates were evaluated. Clinical and radiological (CD US) controls were performed 1 day, 7 days, 1 month, and 6 months after the procedure and once a year thereafter, with a mean follow-up of 16 months (range, 6–25 months). ResultsTechnical success and primary occlusion were achieved in all patients with no adverse events. During the follow-up period, CD US demonstrated partial recanalization and symptom recurrence in 2 patients (18%), 14 and 18 months after the initial procedure. These 2 patients had a second ablation procedure with no recanalization or symptom recurrence during the subsequent follow-up period. ConclusionsMOCA is feasible and appears to be a safe and effective technique for treatment of varicose veins in pediatric patients with KTS.

Topographical anatomy of the tentorium cerebelli and venous confluences in human midterm fetuses

Early development of veins and sinuses at and around the posterior cranial fossa seemed not to be shown by photographs except for our recent study (Ann Anat, 2020). Examination of histological sections of 38 fetuses at 10–16 weeks gestational age (GA) demonstrated that: (1) the superior petrosal sinus passed posterosuperiorly through the tentorium cerebelli and, distant and lateral to both the cerebellum and internal ear, drained into the transverse sinus; (2) the superior sagittal sinus was underdeveloped, and the inferior sagittal sinus was not yet evident; (3) the straight sinus (STS) originated from a joining of the bilateral pial veins from the lateral ventricular choroid plexus, passed through the inferoposterior part of the falx cerebri, reached the initial confluens sinuum, and then divided into the bilateral transverse sinuses. The STS origin was immediately behind the pineal body, and near the inferoposterior end of the third ventricle. The falx had a thick attachment to the tentorium below the entire course of the STS and was behind other parts of the brain. Therefore, the development and growth of the posterior dural system seemed to be independent from brain growth, and occurred well before the cerebellum grew to fill the posterior cranial fossa. A basic configuration of intracranial veins and sinuses, including embryonic transient veins (such as the vena capitis prima) seemed to be established by venous return from the choroid plexus and cranial wall, without greatly increasing the abundance of neuronal or glial cells in the brain.